Physiology chapters
Membrane potential and ion channels
Why the inside of a cell is negative at rest, how equilibrium potentials are worked out, the role of the sodium-potassium pump, and the types of ion channel (leak, voltage-gated, ligand-gated and NMDA).
- At rest the inside of a nerve is about −70 mV (large nerve fibres about −90 mV), mainly because the membrane is far more permeable to potassium than to sodium.
- Each ion has an equilibrium (Nernst) potential: K+ about −94 mV, Na+ about +61 mV; the resting potential lies close to the K+ value.
- Channels are leak (always open), voltage-gated, or ligand-gated; the NMDA receptor needs both glutamate and depolarisation to open.
On this page
Overview
Every cell has a voltage across its membrane, the membrane potential. In nerve and muscle (excitable tissues), this voltage can change rapidly to carry signals.
To understand action potentials, synapses and the heart, you first need to know why the inside is negative at rest and how ion channels let ions move.
Ion concentrations
| Ion | Inside (approx.) | Outside (approx.) |
|---|---|---|
| K+ | 140 mmol/L | 4 mmol/L |
| Na+ | 14 mmol/L | 142 mmol/L |
| Cl− | 4–10 mmol/L | 103 mmol/L |
| Ca2+ | Very low (about 0.0001 mmol/L) | 2.4 mmol/L |
These gradients are kept up by the sodium-potassium pump.
Diffusion potential and the Nernst equation
If a membrane lets only K+ through, K+ diffuses out down its concentration gradient. It leaves negative charges (proteins) behind, so the inside becomes negative. This negativity pulls K+ back. When the electrical pull balances the concentration push, there is no net movement.
The voltage at which this balance occurs is the equilibrium (Nernst) potential for that ion.
Nernst equation (at body temperature, for a univalent ion):
EMF (mV) = ± 61 × log (concentration inside / concentration outside)
The sign is negative for positive ions.
| Ion | Equilibrium potential (approx.) |
|---|---|
| K+ | −94 mV |
| Na+ | +61 mV |
| Cl− | About −70 to −90 mV |
| Ca2+ | About +120 mV or more |
The equilibrium potential is the membrane voltage at which there is no net movement of an ion, because the electrical and chemical forces are equal and opposite.
The Goldman equation
The real membrane is permeable to several ions. The Goldman (Goldman-Hodgkin-Katz) equation gives the membrane potential from the concentrations of Na+, K+ and Cl− and the membrane's permeability to each.
The more permeable the membrane is to an ion, the closer the membrane potential moves to that ion's equilibrium potential.
The resting membrane potential
In large nerve fibres the resting potential is about −90 mV; in many neurons it is about −65 to −70 mV. Three things produce it:
- K+ diffusion through leak channels: the biggest contributor. At rest the membrane is about 100 times more permeable to K+ than to Na+.
- A little Na+ leaks in, making the potential slightly less negative than E(K+).
- The Na-K pump adds a small extra negativity (about −4 mV).
The resting potential is close to the K+ equilibrium potential because, at rest, the membrane is far more permeable to K+.
The Na-K pump contributes only a small part of the resting potential directly. Its main role is to maintain the concentration gradients that make the potential possible.
The sodium-potassium pump
- Pumps 3 Na+ out and 2 K+ in for each ATP used.
- It is an active transport (Na+/K+-ATPase).
- Because it moves more positive charge out than in, it is electrogenic: it makes the inside slightly more negative.
- It also helps control cell volume; if it stops, cells swell.
- Digoxin inhibits it (in the heart).
Effect of potassium changes
The resting potential depends mostly on the K+ gradient.
- Hyperkalaemia: less K+ gradient → resting potential becomes less negative (depolarised). At first cells are more excitable; with marked hyperkalaemia, sodium channels become inactivated and cells become less excitable. This is why severe hyperkalaemia causes muscle weakness and dangerous heart rhythms.
- Hypokalaemia: bigger gradient → resting potential becomes more negative (hyperpolarised); cells are harder to excite, causing weakness.
See the action potential page for the effect of calcium.
Ion channels
Ion channels are proteins that form pores through the membrane. They are selective for particular ions.
Leak channels
Always open. The most important are K+ leak channels, which set the resting potential.
Voltage-gated channels
Open or close when the membrane voltage changes.
- Voltage-gated Na+ channel: has two gates. The activation gate opens rapidly on depolarisation; the inactivation gate closes a little later. It cannot reopen until the membrane repolarises. This is the basis of the action potential and the refractory period.
- Voltage-gated K+ channel: opens slowly on depolarisation and lets K+ out to repolarise the membrane.
- Voltage-gated Ca2+ channels: important in the heart, smooth muscle and nerve terminals (transmitter release).
Ligand-gated channels
Open when a chemical (ligand) binds.
- Nicotinic acetylcholine receptor at the neuromuscular junction: lets Na+ in (and K+ out).
- GABA-A and glycine receptors: let Cl− in, causing inhibition.
- AMPA and NMDA glutamate receptors.
The NMDA receptor
A glutamate receptor with special features:
- It needs glutamate (and the co-agonist glycine) to bind.
- At rest, its pore is blocked by Mg2+. The block is removed only when the membrane is already depolarised (usually by AMPA receptors).
- When open, it lets Ca2+ (and Na+) into the cell.
The NMDA receptor opens only when glutamate binds and the membrane is depolarised, removing the magnesium block. The Ca2+ entry triggers long-term potentiation, the basis of learning and memory.
Too much NMDA activity lets in too much calcium and can kill neurons (excitotoxicity), for example after a stroke. Ketamine blocks the NMDA receptor.
Mechanically gated channels
Open when the membrane is stretched; found in touch receptors and the hair cells of the ear.
Clinical relevance
Hyperkalaemia
How it happens: kidney failure, potassium-sparing drugs, cell breakdown.
What you see: muscle weakness and cardiac arrhythmias, from depolarisation and sodium channel inactivation. Calcium is given to stabilise the heart membrane.
Channelopathies
How it happens: inherited faults in ion channels.
What you see: examples include cystic fibrosis (chloride channel), some epilepsies, periodic paralysis and long QT syndrome.
Typical questions: the definition of an equilibrium potential, the values for K+ and Na+, why the resting potential is close to E(K+), the role and stoichiometry of the Na-K pump, the effect of hyperkalaemia on the resting potential, the two gates of the sodium channel, and the magnesium block of the NMDA receptor.
Quick revision
- K+ high inside; Na+ high outside.
- E(K+) about −94 mV; E(Na+) about +61 mV.
- Resting potential near E(K+) because K+ permeability is about 100 times that of Na+.
- Na-K pump: 3 Na+ out, 2 K+ in; electrogenic; maintains gradients.
- Hyperkalaemia depolarises; hypokalaemia hyperpolarises.
- Na+ channel: activation and inactivation gates.
- NMDA: glutamate + depolarisation; Mg2+ block; Ca2+ entry; memory.
Written by The House Job from standard physiology references (Guyton and Hall Textbook of Medical Physiology; BRS Physiology).
FAQ
What is the resting membrane potential of a large nerve fibre?
About −90 mV in Guyton's teaching; many neurons rest at about −65 to −70 mV.
Why is the resting membrane potential negative?
Mainly because K+ diffuses out through leak channels, leaving negative charges inside, and the membrane is much more permeable to K+ than to Na+.
What is the Nernst potential?
The membrane voltage at which an ion's concentration gradient is exactly balanced by the electrical force, so there is no net movement.
What blocks the NMDA receptor at rest?
Magnesium ions in its channel.